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Peer-reviewedCC BYFrontiers in physiology

Functional assessment of experimental lymphedema: a focused mini-review of animal models and measurement methods

  1. 1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , , ,
  2. 2George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology , , ,

Abstract

Lymphedema is a chronic progressive disease resulting from impaired lymphatic transport. A wide range of animal models has been developed to study their pathophysiology, yet how well lymphatic function is measured within these models has received comparatively little attention. This mini-review organizes assessment methodologies into three complementary tiers: Tier 1 covers morphological and indirect outcome measures, including volumetric quantification and histological assessment; Tier 2 covers imaging-based approaches, including near-infrared fluorescence lymphangiography, radionuclide lymphoscintigraphy, and magnetic resonance lymphangiography; and Tier 3 covers direct physiological measurement of physical quantities such as intraluminal pressure, lymphatic conductance, and albumin transport rate. Surveying primary studies across seven species, we identify a recurring mismatch between the species most commonly used for lymphedema modeling and those in which the most informative measurements are technically accessible. The most accessible endpoints tend to reflect late-stage tissue consequences rather than early pumping dysfunction, imaging readouts remain constrained to relative dye intensity rather than true physical flow quantities, and direct physiological measurement is sparse and limited to single time points. For acquired secondary lymphedema, the rat hindlimb model paired with quantitative longitudinal imaging and vessel-level analysis offers a balanced platform, whereas genetic mouse models remain preferable for congenital disease and large-animal models for microsurgical and clinical-scale intervention studies; a cross-tabulation by species and measurement tier is provided to guide model and assessment selection.

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BibTeX
@article{hsu2026functional,
  title = {{Functional assessment of experimental lymphedema: a focused mini-review of animal models and measurement methods}},
  author = {Shao-Yun Hsu and James Brandon Dixon and Zhanna Nepiyushchikh},
  journal = {Frontiers in physiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphys.2026.1912564},
  url = {https://europepmc.org/article/PMC/PMC13725262},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Functional assessment of experimental lymphedema: a focused mini-review of animal models and measurement methods
AU  - Shao-Yun Hsu
AU  - James Brandon Dixon
AU  - Zhanna Nepiyushchikh
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in physiology
DO  - 10.3389/fphys.2026.1912564
UR  - https://europepmc.org/article/PMC/PMC13725262
AB  - Lymphedema is a chronic progressive disease resulting from impaired lymphatic transport. A wide range of animal models has been developed to study their pathophysiology, yet how well lymphatic function is measured within these models has received comparatively little attention. This mini-review organizes assessment methodologies into three complementary tiers: Tier 1 covers morphological and indirect outcome measures, including volumetric quantification and histological assessment; Tier 2 covers imaging-based approaches, including near-infrared fluorescence lymphangiography, radionuclide lymphoscintigraphy, and magnetic resonance lymphangiography; and Tier 3 covers direct physiological measurement of physical quantities such as intraluminal pressure, lymphatic conductance, and albumin transport rate. Surveying primary studies across seven species, we identify a recurring mismatch between the species most commonly used for lymphedema modeling and those in which the most informative measurements are technically accessible. The most accessible endpoints tend to reflect late-stage tissue consequences rather than early pumping dysfunction, imaging readouts remain constrained to relative dye intensity rather than true physical flow quantities, and direct physiological measurement is sparse and limited to single time points. For acquired secondary lymphedema, the rat hindlimb model paired with quantitative longitudinal imaging and vessel-level analysis offers a balanced platform, whereas genetic mouse models remain preferable for congenital disease and large-animal models for microsurgical and clinical-scale intervention studies; a cross-tabulation by species and measurement tier is provided to guide model and assessment selection.
SN  - 1664-042X
ER  -